Sacubitril 97 mg and Valsartan 103 mg Film-coated Tablets Relative to Entresto 97 mg/103 mg Film-coated Tablets

NCT06248112 | Unknown Phase 1

• 1 other identifier: SAV-035-23
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study is to compare the rate and extent of absorption of a generic formulation with that of a reference for mulation when given as equal labeled dose. The study will be a randomized, open-label, single oral dose, full replicated crossover design with four-period, two-treatment, and two-sequence under fasting condition and at least 14 days washout period between the doses.

Conditions

Healthy Subjects

Keywords

Bioequivalence Sacubitril 97 mg and Valsartan 103 mg film-coated tablets

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC 0-t)

  pre-dose (0.000 hour) and at 0.083, 0.167, 0.333, 0.500, 0.670, 0.830, 1.000, 1.330, 1.670, 2.000, 2.500, 3.000, 3.500, 4.000, 5.000, 6.000, 8.000, 10.000, 12.000, 16.000, 24.000, 36.000 and 48.000 hours post-dose

  Blood samples will be collected for PK an pre-dose and at 0.083, 0.167, 0.333, 0.500, 0.670, 0.830, 1.000, 1.330, 1.670, 2.000, 2.500, 3.000, 3.500, 4.000, 5.000, 6.000, 8.000, 10.000, 12.000, 16.000, 24.000, 36.000 and 48.000 hours post-dose

• Maximal measured plasma concentration (Cmax)

  pre-dose (0.000 hour) and at 0.083, 0.167, 0.333, 0.500, 0.670, 0.830, 1.000, 1.330, 1.670, 2.000, 2.500, 3.000, 3.500, 4.000, 5.000, 6.000, 8.000, 10.000, 12.000, 16.000, 24.000, 36.000 and 48.000 hours post-dose

  Blood samples will be collected for PK an pre-dose and at 0.083, 0.167, 0.333, 0.500, 0.670, 0.830, 1.000, 1.330, 1.670, 2.000, 2.500, 3.000, 3.500, 4.000, 5.000, 6.000, 8.000, 10.000, 12.000, 16.000, 24.000, 36.000 and 48.000 hours post-dose

Secondary Outcomes (1)

• Number of subjects with adverse events

  Approximately the day 14 after the last visit

Study Arms (2)

Sequence 1-Sacubitril and Valsartan test product and then reference product

EXPERIMENTAL

Participants will receive treatment 1 in period 1 and treatment 2 in period 2. Where treatment 1= Sacubitril 97 mg and Valsartan 103 mg test product, treatment 2= Sacubitril 97 mg and Valsartan 103 mg reference product.

Drug: Sacubitril and Valsartan-Test product

Sequence 2-Sacubitril and Valsartan reference product and then test product

EXPERIMENTAL

Participants will receive treatment 2 in period 1 and treatment 1 in period 2. Where treatment 1= Sacubitril 97 mg and Valsartan 103 mg test product, treatment 2= Sacubitril 97 mg and Valsartan 103 mg reference product.

Drug: Sacubitril and Valsartan-Reference product

Interventions

Sacubitril and Valsartan-Test product DRUG

Test-Product: Sacubitril 97 mg and Valsartan 103 mg film-coated tablets Manufactured by: Hetero Labs Ltd., India

Sequence 1-Sacubitril and Valsartan test product and then reference product

Sacubitril and Valsartan-Reference product DRUG

Reference-product: ENTRESTOTM (Film-Coated Tablets) 97/103 mg Manufactured by: Novartis Singapore Pharmaceutical Manufacturing Pte. Ltd., Singapore for Novartis Pharma AG, Basle, Switzerland

Sequence 2-Sacubitril and Valsartan reference product and then test product

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willingness to provide written informed consent prior to participate in the study.
• Healthy Thai subjects are between 18 to 55 years of age.
• The Body Mass Index (BMI) ranges from 18.5 to 30 kg/m2.
• Comprehensive of the nature and purpose of the study and compliance with the requirement of the entire protocol and allow investigators to draw 7 mL of blood for monitoring subjects' safety after the completion of the study.
• Negative urine pregnancy test for women and no breast-feeding.
• Absence of significant diseases or clinically significant abnormal laboratory values on the laboratory evaluations, medical history or surgery during the screening. Some of the laboratory values e.g. Complete blood count etc. that out of the normal range will be carefully considered by physician.

You may not qualify if:

• History or evidence of allergy or hypersensitivity to Sacubitril/Valsartan or any related drugs or any of the excipients of this product.
• Subject with B.P. is Systolic B.P \< 100, ≥140 mm/Hg, Diastolic B.P \< 70, ≥90 mm/Hg or pulse rate \> 100 beats per minute.
• Serum bilirubin greater than 1.5 times the upper limit of reference range (ULRR).\*
• Serum creatinine greater than 1.5 times the upper limit of reference range (ULRR).\*
• Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater than 2 times the upper limit of reference range (ULRR).\*
• Positive of hepatitis B or C virus.
• Have more than one abnormal EKG, which is considered as clinically significant.\*
• History or evidence of angioedema related to previous ACE inhibitor or ARB therapy.
• History or evidence of heart, renal, hepatic disease, pulmonary obstructive disease, bronchial asthma, hypertension or glaucoma.
• History or evidence of gastrointestinal disorder likely to influence drug absorption or previous GI surgery other than appendectomy.
• Any major illness in the past 3 months or any significant ongoing chronic medical illness.
• History of psychiatric disorder.
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) and cannot stop at least 2 days before the study drug administration and until the completion of each period of the study.
• History of usually smoking (more than 10 cigarettes per day within past 1 year), if moderate smokers (less than 10 cigarettes per day) cannot stop at least 7 days before the study drug administration and until the completion of the study.
• High caffeine consumption (more than 5 cups of coffee or tea per day) and cannot stop at least 2 days before the study drug administration and until the completion of each period of the study.

Sponsors & Collaborators

• Bio-innova Co., Ltd: lead

MeSH Terms

Interventions

sacubitril

Central Study Contacts

Sasitorn Kittivoravitkul, Ph.D.

CONTACT

022549008; sasitorn_k@bio-innova.com

Somkiat Tatritorn, M.D.

CONTACT

022549008; somkiat_t@bio-innova.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 8, 2024
• Study Start: May 6, 2024
• Primary Completion: June 22, 2024
• Study Completion: July 6, 2024
• Last Updated: February 8, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share